Many of the drugs which act upon the central nervous system to alter behavior also profoundly affect the functions of monoaminergic neurons both in the brain and in peripheral tissues. The effects of the acute administration of these drugs have been studied extensively. However, studies currently in progress indicate that the actions of many of these drugs differ considerably depending upon whether they are administered acutely or are administered repeatedly over a prolonged period of time. for example, the repeated administration of both the narcotic analgesics and the amphetamines results in the development of tolerance to certain specific effects of these drugs. The changes in the effects of the amphetamines upon brain catecholamine content are correlated with changes in the activity of tyrosine hydroxylase in specific areas of the central nervous system. In addition, physical dependence upon and tolerance to the narcotic analgesics are well correlated with changes in brain catecholamine synthesis. The purpose of the proposed project is to continue studies which compare the effects of acute and chronic administration of certain drugs which affect behavior upon the uptake, synthesis, storage, release and metabolism of biogenic amines in the braan and by adrenergic neurons in peripheral tissues such as heart, spleen, adrenals and vas deferens. Three classes of drugs are being studied: the psychomotor stimulants, the tricyclic antidepressants, and the narcotic analgesics.